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Sub-acute Cerebral Microhemorrhages Induced by Lipopolysaccharide Injection in Rats
Published on: October 17, 2018
Post-treatment With Qing-Ying-Tang, a Compound Chinese Medicine Relives Lipopolysaccharide-Induced Cerebral
Hao-Min Wang1,2,3,4,5,6, Ping Huang2,3,4,5,6, Quan Li2,3,4,5,6
1Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.
Abstract:
Objective: Lipopolysaccharide (LPS) causes microvascular dysfunction, which is a key episode in the pathogenesis of endotoxemia. This work aimed to investigate the effect of Qing-Ying-Tang (QYT), a compound Chinese medicine in cerebral microcirculation disturbance and brain damage induced by LPS. Methods: Male C57/BL6 mice were continuously transfused with LPS (7.5 mg/kg/h) through the left femoral vein for 2 h. QYT (14.3 g/kg) was given orally 2 h after LPS administration. The dynamics of cerebral microcirculation were evaluated by intravital microscopy. Brain tissue edema was assessed by brain water content and Evans Blue leakage. Cytokines in plasma and brain were evaluated by flow cytometry. Confocal microscopy and Western blot were applied to detect the expression of junction and adhesion proteins, and signaling proteins concerned in mouse brain tissue. Results: Post-treatment with QYT significantly ameliorated LPS-induced leukocyte adhesion to microvascular wall and albumin leakage from cerebral venules and brain tissue edema, attenuated the increase of MCP-1, MIP-1α, IL-1α, IL-6, and VCAM-1 in brain tissue and the activation of NF-κB and expression of MMP-9 in brain. QYT ameliorated the downregulation of claudin-5, occludin, JAM-1, ZO-1, collagen IV as well as the expression and phosphorylation of VE-cadherin in mouse brain. Conclusions: This study demonstrated that QYT protected cerebral microvascular barrier from disruption after LPS by acting on the transcellular pathway mediated by caveolae and paracellular pathway mediated by junction proteins. This result suggests QYT as a potential strategy to deal with endotoxemia.
Insights
Qing-Ying-Tang (QYT) protects the brain from lipopolysaccharide (LPS)-induced damage by stabilizing the cerebral microvascular barrier. This Chinese medicine reduces inflammation and edema, offering a potential treatment for endotoxemia.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Lipopolysaccharide (LPS) induces microvascular dysfunction, a critical factor in endotoxemia pathogenesis.
- Cerebral microcirculation disturbances and brain damage are significant consequences of LPS exposure.
Purpose of the Study:
- To investigate the protective effects of Qing-Ying-Tang (QYT), a compound Chinese medicine, against LPS-induced cerebral microcirculation impairment and brain damage.
- To elucidate the mechanisms underlying QYT's action on the cerebral microvascular barrier.
Main Methods:
- Male C57/BL6 mice were treated with LPS to induce endotoxemia.
- QYT was administered orally as a post-treatment intervention.
- Cerebral microcirculation, brain edema, cytokine levels, and protein expression (junctional, adhesion, signaling) were assessed using intravital microscopy, biochemical assays, flow cytometry, confocal microscopy, and Western blot.
Main Results:
- QYT significantly reduced LPS-induced leukocyte adhesion and albumin leakage in cerebral venules, mitigating brain tissue edema.
- QYT attenuated pro-inflammatory cytokine levels (MCP-1, MIP-1α, IL-1α, IL-6) and VCAM-1 expression in the brain.
- QYT inhibited NF-κB activation and MMP-9 expression, while restoring the expression of tight junction proteins (claudin-5, occludin, JAM-1, ZO-1), collagen IV, and VE-cadherin.
Conclusions:
- QYT protects the cerebral microvascular barrier integrity against LPS-induced disruption.
- The protective mechanism involves both transcellular (caveolae-mediated) and paracellular (junction protein-mediated) pathways.
- QYT demonstrates potential as a therapeutic strategy for managing endotoxemia.

